Topotecan-Hydrochloride-SKF-104864A-Hydrochloride-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETopotecan HydrochlorideCat. No.: HY-13768ACAS No.: 119413-54-6Synonyms: SKF 104864A (Hydrochloride); NSC 609669 (Hydrochloride)分式: CHClNO分量: 457.91作靶点: Topoisomerase; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy储存式: 4C, protec

2、t from light* In solvent : -80C, 6 months; -20C, 1 month (protect fromlight)溶解性数据体外实验 DMSO : 15.3 mg/mL (33.41 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.1838 mL 10.9192 mL 21.8384 mL5 mM 0.4368 mL 2.1838 mL 4.3677 mL10 mM 0.2184 mL 1.0919 mL 2.1838 mL请根据产品在

3、不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Topotecan Hydrochloride (SKF 104864A Hydrochloride)是具有抗癌活性的 拓扑异构酶I 抑制剂。IC50 & Target Topoisomerase I体外研究Topotecan Hydrochloride (SKF 104864A Hydrochloride) obviously inhibits proliferation of not only humanglioma cells but also glioma stem

4、 cells (GSCs) in a dose- and time-dependent manner. According to the IC50values at 24 h, 3 M of Topotecan Hydrochloride is selected as the optimal administration concentration. In1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEaddition, Topotecan Hydrochloride induces cell cycle arrest in G0/G1 and

5、 S phases and promoted apoptosis.Results show that the cell viability is inhibited by Topotecan Hydrochloride in a dose-dependent manner. 2,20 and 40 M of Topotecan Hydrochloride obviously inhibits the cell viability compared with the controlgroups. The IC50 values of Topotecan Hydrochloride at 24 h

6、 are 2.730.25 M of U251 cells, 2.950.23 Mof U87 cells, 5.460.41 M of GSCs-U251 and 5.950.24 M of GSCs-U87. Thus 3 M of TopotecanHydrochloride is selected as the optimal administration concentration in the subsequent experiments 1.体内研究 NUB-7 metastatic model, the animals belonging to all the 4 groups

7、 are sacrificed after 14 days treatment.Compared with the control, Low dose metronomic (LDM) Topotecan Hydrochloride and TP+Pazopanib (PZ)liver weights are significantly lower in TP+PZ-treated animals, compared with PZ. Microscopic tumors arevisible in the livers of mice belonging to all the groups

8、except TP+PZ confirming the ability of TopotecanHydrochloride+PZ to control liver metastasis. In a previous dose-response study, the daily dose of oralmetronomic Topotecan Hydrochloride (0.5, 1.0, and 1.5 mg/kg) causes greater reduction in microvasculardensity compared with weekly maximum-tolerated

9、dose regimen (7.5 and 15 mg/kg) in an ovarian cancermodel, but the mice treated with 1.5 mg/kg daily, oral Topotecan Hydrochloride show decreased food intake,and a lesser antitumor effect 2.PROTOCOLCell Assay 1 The U251, U87, GSCs-U251 and GSCs-U87 cells are seeded at a density of 2104 cells per wel

10、l in 96-wellplates separately, and incubated for 24 h. Cells are administered with Shikonin and Topotecan Hydrochloride(0.02, 0.2, 2, 20, 40 M). After the treatment, 10 L of cell counting kit-8 (CCK-8) is added into each well foradditional 1-hour incubation at 37C. The optical density (OD) is read w

11、ith a microplate reader at 450 nm 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 For subcutaneous xenograft studies, we used SK-N-BE, SH-SY5Y, KHOS, and RH30. 1106 cells areimplanted subcutaneously into the inguinal fat

12、pad of each of nonobese diabetic/severe combined immunedeficient (NOD/SCID) mice. When tumors reached 0.5 cm in diameter, the animals are randomized into 4groups and treated daily by oral gavage. The animals are grouped as: Control group, LDM Topotecan groupor LDM TP (1 mg/kg Topotecan), Pazopanib g

13、roup or PZ (150 mg/kg Pazopanib) and combination group orTP + PZ (1 mg/kg Topotecan Hydrochloride + 150 mg/kg Pazopanib). To compare pulse Topotecan withLDM TP in KHOS osteosarcoma model, PZ is replaced by weekly oral dose of pulse Topotecan or Pulse TP(15 mg/kg Topotecan). The criteria for endpoint

14、 are tumor sizes exceeding 2.0 cm in diameter or animalsshowing signs of morbidity. The tumor sizes are measured on a daily basis until the endpoint or sacrifice. Thelong (D) and short diameters (d) are measured with calipers. Tumor volume (cm3) is calculated asV=0.5Dd2. When the endpoint is reached

15、 or at the end of the treatment, the animals are sacrificed bycervical dislocation.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE J Exp Clin Cancer Res. 2018 Dec 20;37(1):321. J Mol Med (Berl

16、). 2019 Jun 14. J Virol. 2019 Mar 13. pii: JVI.02230-18.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Zhang FL, et al. PLoS One. 2013 Nov 26;8(11):e81815.Topoisomerase I inhibitors, Shikonin and Topotecan, inhibit growth and induceapoptosis of glioma cells andglioma stem cells.2. Kumar S, et al. Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatricsolid tu